title: Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration.
abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/- mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/- mice was not enhanced. Instead, the Tsc2+/- livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. youko_oobayashi@ajinomoto.com
authors.forename: Yoko
authors.initials: Y
authors.lastname: Obayashi
authors.forename: Jean S
authors.initials: JS
authors.lastname: Campbell
authors.forename: Nelson
authors.initials: N
authors.lastname: Fausto
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Yeung
mesh_terms: D000818:Animals; D001835:Body Weight; D004789:Enzyme Activation; D006498:Hepatectomy; D006579:Heterozygote; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: C000624654:Tsc2 protein, mouse; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride; 5′AMP-activated protein kinase; AEBSF; AMPK; C57BL/6; ERK; GAP; GTPase-activating protein; Lipid; Liver regeneration; MAPK; P70S6K; PH; Rheb; SH; TSC; TSC2; Tuberin; c57 black 6; extracellular signal-regulated kinase; mTOR; mammalian target of rapamycin; mitogen-activated protein kinase; p70 ribosomal S6 kinase; p90 RSK; p90 ribosomal S6 kinase; partial hepatectomy; ras homolog enriched in brain; sham operation; tuberous sclerosis